Vasoactive intestinal polypeptide receptor 2 (VPAC2)

Vasoactive intestinal polypeptide receptor 2 (VPAC2, also known as VIP2R) is a transmembrane receptor in the class B1 GPCR superfamily activated primarily by the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating polypeptide (PACAP). The receptor is expressed extensively in the central and peripheral nervous systems, as well as endocrine tissues. VPAC2 mediates signal transduction via cAMP, affecting processes such as insulin secretion (in a glucose-dependent manner), immune modulation, circadian rhythm, neural development, thermoregulation, and various endocrine and metabolic responses. VPAC2 is considered a therapeutic target for diabetes, autoimmune and inflammatory diseases, cancer, pulmonary arterial hypertension, COPD, and select neuropsychiatric conditions. Drug development has focused on selective agonists (for diabetes) and antagonists (for cancer), with considerable research on its pharmacological modulation, safety profile, and physiological roles.

Other names

VPAC2VIP2RVIPR2vasoactive intestinal peptide receptor type 2vasoactive intestinal peptide receptor 2

Agonists stimulate cAMP production via adenylyl cyclase, leading to downstream activation of PKA, Epac, membrane depolarization, calcium influx, and exocytosis (in pancreatic β-cells for insulin secretion) Immunomodulation: receptor activation affects T-cell differentiation, promotes regulatory T cell expansion, and controls pathogenic signaling in immune cells